Nomura Shosaku, Ito Tomoki, Yoshimura Hideaki, Hotta Masaaki, Nakanishi Takahisa, Fujita Shinya, Nakaya Aya, Satake Atsushi, Ishii Kazuyoshi
First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
J Blood Med. 2018 Jan 19;9:1-7. doi: 10.2147/JBM.S147743. eCollection 2018.
Thrombosis is one of the complications in the clinical course of multiple myeloma (MM). Vascular endothelial cells and/or the hemostatic-coagulatory system are thought to play an important role in thrombosis of MM. In addition to melphalan-prednisone (Mel-P) therapy, several new therapeutic drugs such as lenalidomide or bortezomib have been developed and show effectiveness against MM. However, these new drugs also have risk of therapy-related thrombosis.
We assessed 103 MM patients and 30 healthy controls, using enzyme-linked immunosorbent assays to evaluate five biomarkers: platelet-derived microparticles (PDMP), plasminogen activator inhibitor-1 (PAI-1), high mobility group box protein-1 (HMGB1), endothelial protein C receptor (EPCR), and soluble vascular cell adhesion molecule-1 (sVCAM-1). The effects of Mel-P, bortezomib, and lenalidomide on the plasma concentrations of these biomarkers were investigated.
The plasma concentrations of PDMP, PAI-1, HMGB1, EPCR, and sVCAM-1 were higher in MM patients than in healthy controls. Mel-P, bortezomib, and lenalidomide therapies all reduced biomarker levels after treatment. However, when only patients with higher levels of EPCR were compared, differences were seen between the three therapies in the elevation of PDMP, HMGB1, and PAI-1.
These results suggest that both MM and therapies for MM can induce a hypercoagulable state. The elevated risk of thrombosis conferred by hypercoagulability increases patient morbidity and mortality. Attention should be paid to therapy-related thrombosis when new therapeutic regimens are selected for MM patients.
血栓形成是多发性骨髓瘤（MM）临床病程中的并发症之一。血管内皮细胞和/或止血凝血系统被认为在MM血栓形成中起重要作用。除了美法仑-泼尼松（Mel-P）疗法外，还研发了几种新型治疗药物，如来那度胺或硼替佐米，它们对MM显示出有效性。然而，这些新药也有治疗相关血栓形成的风险。
我们评估了103例MM患者和30名健康对照者，采用酶联免疫吸附测定法评估五种生物标志物：血小板衍生微粒（PDMP）、纤溶酶原激活物抑制剂-1（PAI-1）、高迁移率族蛋白B1（HMGB1）、内皮蛋白C受体（EPCR）和可溶性血管细胞黏附分子-1（sVCAM-1）。研究了Mel-P、硼替佐米和来那度胺对这些生物标志物血浆浓度的影响。
MM患者血浆中PDMP、PAI-1、HMGB1、EPCR和sVCAM-1的浓度高于健康对照者。Mel-P、硼替佐米和来那度胺治疗后均降低了生物标志物水平。然而，仅比较EPCR水平较高的患者时，三种疗法在PDMP, HMGB1和PAI-1升高方面存在差异。
这些结果表明，MM及其治疗均可诱导高凝状态。高凝状态导致的血栓形成风险增加会提高患者的发病率和死亡率。为MM患者选择新的治疗方案时，应注意治疗相关的血栓形成。
